Chemical sensors are devices that detect the presence and/or level of a particular chemical species (an “analyte”) in the air, water, or another medium. There exists high demand for chemical sensor devices able to detect low concentrations of analytes in liquid and/or gaseous phases. Specificity to particular analytes (i.e., the ability of a sensor to distinguish one species from another) is also generally desired.
The threat of chemical attack with aqueous or gas-phase organophosphates has been the motivation for extensive chemical sensor research in recent years. Many existing sensing methods (e.g., electrochemical, surface acoustic wave, colorimetric, fluorescence- and luminescence-based) target fast, portable, and inexpensive recognition. Sensors used to detect vapor phase nerve agent release in populated areas rely on specificity and subsecond response to ensure that the released vapor is accurately identified. For example, existing organophosphate vapor sensors are based on materials (e.g., fluorescent indicators, polymers, metal oxides, and gold nanoparticles) developed for fast recognition of a specific phosphonate or other functional groups. For example, see: Lin, Y.; Lu, F.; Wang, J. Electroanalysis 2004, 16, 145-149; Zhou, Y.; Yu, B.; Shiu, E.; Levon, K. Analytical Chemistry 2004, 76, 2689-2693; Yu, D.; Volponi, J.; Chhabra, S.; Brinker, C. J.; Mulchandani, A.; Singh, A. K. Biosensors & Bioelectronics 2005, 20, 1433-1437; Anitha, K.; Mohan, S. V.; Reddy, S. J. Biosensors & Bioelectronics 2004, 20, 848-856; Simonian, A. L.; Grimsley, J. K.; Flounders, A. W.; Schoeniger, J. S.; Cheng, T. C.; DeFrank, J. J.; Wild, J. R. Analytica Chimica Acta 2001, 442, 15-23; Yang, Y.; Ji, H.-F.; Thundat, T. Journal of the American Chemical Society 2003, 125, 1124-1125; Hartmann-Thompson, C.; Hu, J.; Kaganove, S, N.; Keinath, S. E.; Keeley, D. L.; Dvornic, P. R. Chemistry of Materials 2004, 16, 5357-5364; Pavlov, V.; Xiao, Y.; Willner, I. Nano Letters 2005, 5, 649-653; Zhang, S.-W.; Swager, T. M. Journal of the American Chemical Society 2003, 125, 3420-3421; Jenkins, A. L.; Uy, O. M.; Murray, G. M. Analytical Chemistry 1999, 71, 373-378; Jenkins, A. L.; Yin, R.; Jensen, J. L.; Durst, H. D. Polymeric Materials Science and Engineering 2001, 84, 76-77; Levitsky, I.; Krivoshlykov, S. G.; Grate, J. W. Analytical Chemistry 2001, 73, 3441-3448; Utriainen, M.; Karpanoja, E.; Paakkanen, H. Sensors and Actuators, B: Chemical 2003, B93, 17-24; and Tomchenko, A.; Harmer, G. P.; Marquis, B. Chemical Sensors 2004, 20, 34-35.
Materials research has thus far focused mostly on discovering chemical entities that enable chemical warfare agent recognition, with less effort spent on sensor miniaturization and integration. As a consequence, the current sensors are not specifically designed to fit within existing multiplex vapor detection systems, such as sensor arrays, including electronic noses. Integration into such arrays is important, as array platforms contain several sensor types that can detect a wide spectrum of harmful vapors, and nerve agents represent only a small percentage among them. The ability to detect toxic chemical agents is facilitated by sensors that can identify these agents in a variety of contexts including backgrounds containing high concentrations of non-toxic chemicals.
An “electronic nose system” may be a fluorescence-based array containing thousands of individually optically addressable micron-scale vapor sensors. Dickinson, T. A.; Michael, K. L.; Kauer, J. S.; Walt, D. R. Analytical Chemistry 1999, 71, 2192-2198; and Dickinson, T. A.; White, J.; Kauer, J. S.; Walt, D. R. Nature (London) 1996, 382, 697-700. Each array may be prepared by loading 3-5 μm diameter microbead sensors into 4.5 μm diameter wells, etched into a fiber-optic bundle. This technology is advantageous for multiplexing and accommodating newly developed microsensors for a number of reasons: microbead batches are highly reproducible and inexpensive to fabricate, the sensor library may be expanded at any point in time, individually addressable multiple replicates of different microbead sensor types are accommodated on a highly dense array platform, and the arrays respond to vapors in sub-second times. Albert, K. J.; Walt, D. R. Analytical Chemistry 2000, 72, 1947-1955; and Stitzel, S. E.; Cowen, L. J.; Albert, K. J.; Walt, D. R. Analytical Chemistry 2001, 73, 5266-5271.
A “cross-reactive vapor sensing array”, also referred to as an electronic nose or artificial nose system, is an array where each sensor type is cross-reactive and responds to many vapors. Albert, K. J.; Lewis, N. S.; Schauer, C. L.; Sotzing, G. A.; Stitzel, S. E.; Vaid, T. P.; Walt, D. R. Chemical Reviews (Washington, D.C.) 2000, 100, 2595-2626. Although cross-reactive sensors can respond reversibly hundreds of times, they often delay vapor identification because the data must be evaluated using pattern recognition—a time-consuming process. Bencic-Nagale, S.; Walt, D. R. Analytical Chemistry 2005, 77, 6155-6162. Moreover, difficult vapor discrimination tasks, such as differentiation between nerve agents and their less harmful simulants, may prolong the data processing time; challenging vapor queries often require the extraction of extensive amounts of information from the sensors. Vapor detection tasks necessitating immediate answers should not employ sensors that require lengthy data processing; for such tasks, specific probes are preferable to cross-reactive sensors. Although some specific probes that react with the target vapor irreversibly present a drawback as they may be used only a single time, their rapid response speed and specificity overshadow the disadvantage in having to replace the array after a vapor release has occurred. In such cases, the value of having a rapid responding probe for a rare event makes replacement acceptable as long as the chemistry is designed to provide zero false positive results.
Unfortunately, many previously developed sensors are not sufficiently specific because they detect both reactive and non-reactive simulants; therefore, novel sensors are needed. Recently developed probe compounds have partially overcome the lack of specificity common in many phosphonate warfare sensors, as they react only with phosphonyl halides. Zhang, S.-W.; Swager, T. M. Journal of the American Chemical Society 2003, 125, 3420-3421; Swager, T. M. et al. U.S. Patent Application 2005/0147534; incorporated by reference. Their probe compounds are designed to detect acetylcholinesterase inhibitor phosphonates when they convert into fluorescent esters upon reaction with phosphonyl halides. In addition to specificity, sensitivity, and fast response, these probes are advantageous due to their turn-on behavior upon binding the target analyte. Advantages of turn-on sensors have also been demonstrated with rhodamine derivatives that fluoresce upon selectively reacting with mercury (II) ions. Yang, Y.-K.; Yook, K.-J.; Tae, J. J. Am. Chem. Soc. 2005, 127, 16760-16761. Turn-on sensors are more reliable than turn-off sensors because they are less prone to false positives. Mortellaro, M. A.; Nocera, D. G. Chemtech 1996, 26, 17-23; and Fan, C.; Plaxco, K. W.; Heeger, A. J. Proceedings of the National Academy of Sciences of the United States of America 2003, 100, 9134-9137. False positives are rarely observed with turn-on sensors because, unlike turn-off sensors, high background intensity and photobleaching minimally affect their overall response.